In vitro aflatoxin B1-induced p53 mutations

• Published in: Cancer letters Vol. 199; no. 1; pp. 1 - 7
• Main Authors: Chan, Kin-Tak, Hsientang Hsieh, Dennis Paul, Lung, Maria Li
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 10.09.2003; Elsevier; Elsevier Limited
• Subjects: Aflatoxin B1; Aflatoxin B1 - toxicity; Antineoplastic agents; Base Sequence; Biological and medical sciences; Carcinogens; Cell cycle; Codon - genetics; CpG dinucleotide; Deoxyribonucleic acid; Dinucleoside Phosphates - metabolism; DNA; DNA Methylation; DNA Primers; DNA, Complementary; Genes, p53 - drug effects; Hot spot mutation; Liver cancer; Medical sciences; Methylation; Mutagens; Mutation; p53; Pharmacology. Drug treatments; Plasmids; Plasmids - drug effects; Plasmids - genetics; Polymerase Chain Reaction; Proteins; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Templates, Genetic; Tumors; Yeast; Yeast p53 functional assay; Aflatoxin B1; Hot spot mutation; Methylation; CpG dinucleotide; p53; Yeast p53 functional assay; Yeast; Nucleotide sequence; Dinucleotide; Hot spot; In vitro; Toxin; TP53 Gene; GC rich sequence; Mutation; Tumor suppressor gene
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(03)00337-9

The tumor suppressor gene p53 is commonly mutated with high frequencies at certain hot spots in human cancers. In liver cancers there is an especially high frequency of mutations at codon 249. To study the impact of carcinogen targeting and the role of cytosine methylation on the mutation spectrum, a common liver cancer carcinogen aflatoxin B1 (AFB1), was studied using the p53 cDNA template to examine mutation induction. Subsequent mutations were detected with a yeast p53 functional assay and identified by DNA sequencing. The results indicated that cytosine methylation enhances AFB1-induced guanine mutations at CpG sites. However, no mutations were detected at codon 249.